RRC ID 65495
著者 Yonemori K, Seki N, Kurahara H, Osako Y, Idichi T, Arai T, Koshizuka K, Kita Y, Maemura K, Natsugoe S.
タイトル ZFP36L2 promotes cancer cell aggressiveness and is regulated by antitumor microRNA-375 in pancreatic ductal adenocarcinoma.
ジャーナル Cancer Sci
Abstract Due to its aggressive nature, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and hard-to-treat malignancies. Recently developed targeted molecular strategies have contributed to remarkable improvements in the treatment of several cancers. However, such therapies have not been applied to PDAC. Therefore, new treatment options are needed for PDAC based on current genomic approaches. Expression of microRNA-375 (miR-375) was significantly reduced in miRNA expression signatures of several types of cancers, including PDAC. The aim of the present study was to investigate the functional roles of miR-375 in PDAC cells and to identify miR-375-regulated molecular networks involved in PDAC aggressiveness. The expression levels of miR-375 were markedly downregulated in PDAC clinical specimens and cell lines (PANC-1 and SW1990). Ectopic expression of miR-375 significantly suppressed cancer cell proliferation, migration and invasion. Our in silico and gene expression analyses and luciferase reporter assay showed that zinc finger protein 36 ring finger protein-like 2 (ZFP36L2) was a direct target of miR-375 in PDAC cells. Silencing ZFP36L2 inhibited cancer cell aggressiveness in PDAC cell lines, and overexpression of ZFP36L2 was confirmed in PDAC clinical specimens. Interestingly, Kaplan-Meier survival curves showed that high expression of ZFP36L2 predicted shorter survival in patients with PDAC. Moreover, we investigated the downstream molecular networks of the miR-375/ZFP36L2 axis in PDAC cells. Elucidation of tumor-suppressive miR-375-mediated PDAC molecular networks may provide new insights into the potential mechanisms of PDAC pathogenesis.
巻・号 108(1)
ページ 124-135
公開日 2017-1-1
DOI 10.1111/cas.13119
PMID 27862697
PMC PMC5276842
MeSH Adult Aged Aged, 80 and over Carcinoma, Pancreatic Ductal / genetics* Carcinoma, Pancreatic Ductal / metabolism Carcinoma, Pancreatic Ductal / pathology* Cell Line, Tumor Cell Movement Cell Proliferation Female Gene Expression Regulation, Neoplastic Gene Silencing* Humans Immunohistochemistry Male MicroRNAs / genetics* Middle Aged Neoplasm Invasiveness Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology* Transcription Factors / biosynthesis Transcription Factors / deficiency Transcription Factors / genetics* Transcription Factors / metabolism*
IF 4.966
リソース情報
ヒト・動物細胞 PANC-1(RCB2095)